Patient Derived Organoids to Model Rare Prostate Cancer Phenotypes

Overview

Journal Nat Commun

Specialty Biology

Date 2018 Jun 21

PMID 29921838

Citations 193

Authors

Loredana Puca

Rohan Bareja

Davide Prandi

Reid Shaw

Matteo Benelli

Wouter R Karthaus

Judy Hess

Michael Sigouros

Adam Donoghue

Myriam Kossai

Dong Gao

Joanna Cyrta

Verena Sailer

Aram Vosoughi

Chantal Pauli

Yelena Churakova

Cynthia Cheung

Lesa Dayal Deonarine

Terra J McNary

Rachele Rosati

Scott T Tagawa

David M Nanus

Juan Miguel Mosquera

Charles L Sawyers

Yu Chen

Giorgio Inghirami

Rema A Rao

Carla Grandori

Olivier Elemento

Andrea Sboner

Francesca Demichelis

Mark A Rubin

Himisha Beltran

Affiliations

Soon will be listed here.

Abstract

A major hurdle in the study of rare tumors is a lack of existing preclinical models. Neuroendocrine prostate cancer is an uncommon and aggressive histologic variant of prostate cancer that may arise de novo or as a mechanism of treatment resistance in patients with pre-existing castration-resistant prostate cancer. There are few available models to study neuroendocrine prostate cancer. Here, we report the generation and characterization of tumor organoids derived from needle biopsies of metastatic lesions from four patients. We demonstrate genomic, transcriptomic, and epigenomic concordance between organoids and their corresponding patient tumors. We utilize these organoids to understand the biologic role of the epigenetic modifier EZH2 in driving molecular programs associated with neuroendocrine prostate cancer progression. High-throughput organoid drug screening nominated single agents and drug combinations suggesting repurposing opportunities. This proof of principle study represents a strategy for the study of rare cancer phenotypes.

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